This invention relates to novel derivatives of 9-deoxo-9a-aza-9a-homoerythromycin A and of its 4"-epimer useful as antibacterial agents, to intermediates therefor, and to processes for preparation of said derivatives and said intermediates. More particularly it relates to cyclic ether derivatives of 9-deoxo-9a-aza-9a-homoerythromycin A and of its 4"-epimer, to pharmaceutically acceptable acid addition salts thereof and the use of said compounds as antibacterial agents, to intermediates therefor, and to processes for their preparation.
Erythromycin A is a macrolide antibiotic produced by fermentation and described in U.S. Pat. No. 2,653,899. Numerous derivatives of erythromycin A have been prepared in efforts to modify its biological and/or pharmacodynamic properties. Erythromycin A esters with mono- and dicarboxylic acids are reported in Antibiotics Annual, 1953-1954, Proc. Symposium Antibiotics (Washington, D.C.), pages 500-513 and 514-521, respectively. U.S. Pat. No. 3,417,077 describes the cyclic carbonate ester of erythromycin A, the reaction product of erythromycin A and ethylene carbonate, as an active antibacterial agent.
U.S. Pat. No. 4,328,334, issued May 4, 1982 describes 9-deoxo-9a-aza-9a-homoerythromycin A and refers to it by the name 11-aza-10-deoxo-10-dihydroerythromycin A. Since said compound is a ring expanded (homo) derivative of erythromycin A, nitrogen (aza) being the additional atom of the ring system, the nomenclature 9-deoxo-9a-aza-9a-homoerythromycin A is preferred for the parent ring system of the compounds of this invention.
Belgian Patent No. 892,357, published July 1, 1982, and its British counterpart, Application No. 2,094,293A, published Sept. 15, 1982, disclose the N-methyl derivative of 9-deoxo-9a-aza-9a-homoerythromycin A, as does my copending U.S. application Ser. No. 441,981, filed Nov. 15, 1982, which claims priority from U.S. application Ser. No. 399,401, filed July 19, 1982. The 4"-epimer of said N-methyl derivative is the subject of my copending U.S. application Ser. No. 441,979, filed Nov. 15, 1982. U.S. Pat. No. 4,382,085, issued May 3, 1983 describes 4"-epi erythromycin A; i.e., the 4"--OH group has the axial configuration. The 4"--OH in erythromycin A has the equatorial configuration.